title: Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children.
abstract: Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000 AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS.
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Ashima
authors.initials: A
authors.lastname: Gulati
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Savita
authors.initials: S
authors.lastname: Saini
authors.affiliation: Laboratoire d'Immunologie, Hôpital Européen Georges Pompidou, INSERM UMRS 872, team 13 and Paris Descartes University, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Blanc
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Aarti
authors.initials: A
authors.lastname: Gupta
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Bahadur Singh
authors.initials: BS
authors.lastname: Gurjar
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Himanshi
authors.initials: H
authors.lastname: Saini
authors.affiliation: Laboratoire d'Immunologie, Hôpital Européen Georges Pompidou, INSERM UMRS 872, team 13 and Paris Descartes University, Paris, France.
authors.forename: Shambhuprasad T
authors.initials: ST
authors.lastname: Kotresh
authors.affiliation: Department of Pediatrics, BJ Wadia Hospital for Children, Mumbai, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Ali
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Bhatia
authors.affiliation: Department of Pediatrics, BJ Wadia Hospital for Children, Mumbai, India.
authors.forename: Alpana
authors.initials: A
authors.lastname: Ohri
authors.affiliation: Chacha Nehru Bal Chikitsalaya, New Delhi, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Pediatrics, Christian Medical College, Vellore, India.
authors.forename: Indira
authors.initials: I
authors.lastname: Agarwal
authors.affiliation: Department of Nephrology, Fortis Hospitals, New Delhi, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gulati
authors.affiliation: Division of Pediatric Nephrology, Sir Ganga Ram Hospital, New Delhi, India.
authors.forename: Kanav
authors.initials: K
authors.lastname: Anand
authors.affiliation: Department of Pediatric Nephrology, Mehta Children's Hospital, Chennai, India.
authors.forename: M
authors.initials: M
authors.lastname: Vijayakumar
authors.affiliation: Institute of Child Health, Kolkata, India.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Sinha
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Sidharth
authors.initials: S
authors.lastname: Sethi
authors.affiliation: Laboratoire d'Immunologie, Hôpital Européen Georges Pompidou, INSERM UMRS 872, team 13 and Paris Descartes University, Paris, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Salmona
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Anna
authors.initials: A
authors.lastname: George
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Vineeta
authors.initials: V
authors.lastname: Bal
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Geetika
authors.initials: G
authors.lastname: Singh
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Dinda
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Hari
authors.affiliation: National Institute of Immunology, New Delhi, India.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Rath
authors.affiliation: Laboratoire d'Immunologie, Hôpital Européen Georges Pompidou, INSERM UMRS 872, team 13 and Paris Descartes University, Paris, France.
authors.forename: Marie-Agnes
authors.initials: MA
authors.lastname: Dragon-Durey
authors.affiliation: Division of Nephrology, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Arvind
authors.initials: A
authors.lastname: Bagga
mesh_terms: D000367:Age Factors; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood*; D001379:Azathioprine / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000235:genetics / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003180:Complement C3b Inactivator Proteins / Q000235:genetics / Q000276:immunology*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D017353:Gene Deletion; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D006720:Homozygote; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007194:India; D007223:Infant; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D010951:Plasma Exchange / Q000009:adverse effects; D011239:Prednisolone / Q000627:therapeutic use; D012008:Recurrence; D012307:Risk Factors; D000069283:Rituximab; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D015415:Biomarkers; D001798:Blood Proteins; C517621:CFHR1 protein, human; C105970:CFHR3 protein, human; D003180:Complement C3b Inactivator Proteins; D007166:Immunosuppressive Agents; D000069283:Rituximab; D003520:Cyclophosphamide; D011239:Prednisolone; D009173:Mycophenolic Acid; D001379:Azathioprine